scholarly journals Identification of glycoprotein Ib as a target for autoantibody in idiopathic (autoimmune) thrombocytopenic purpura

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 310-315 ◽  
Author(s):  
NS Szatkowski ◽  
TJ Kunicki ◽  
RH Aster
Keyword(s):  
Direct Evidence ◽  
Protein A ◽  
Normal Subjects ◽  
Platelet Membrane ◽  
Staphylococcal Protein A ◽  
Glycoprotein Ib ◽  
Thrombocytopenic Purpura ◽  
One Dimensional ◽  
Rocket Electrophoresis ◽  
And Control

Abstract An antibody (DIL) from a patient with idiopathic thrombocytopenic purpura (ITP) was shown to have autospecificity on the basis of reactions with autologous platelets that were identical to those obtained with platelets from normal subjects. DIL antibody also reacted strongly in an immunofluorescence test with platelets from a patient with Glanzmann's thrombasthenia, but failed to react with platelets from a patient with the Bernard-Soulier syndrome who was known to be deficient in glycoprotein Ib (GPIb). Purified GPIb and control platelets, but not Bernard-Soulier platelets, inhibited the lytic activity of DIL. Using the GPIb-specific monoclonal antibody AP1 and one-dimensional rocket electrophoresis into gels containing rabbit antihuman platelet membrane antibody, it was shown that staphylococcal protein A-Sepharose beads coated with DIL antibody selectively remove GPIb from solubilized platelet preparations. By crossed immunoelectrophoresis it was found that DIL recognizes a determinant on GPIb on the membrane side of the cleavage site of the platelet calcium- activated protease (calpain). These studies provide direct evidence for binding of a platelet autoantibody to a determinant on GPIb relatively close to the site of insertion of this protein into the platelet membrane.

scholarly journals Identification of glycoprotein Ib as a target for autoantibody in idiopathic (autoimmune) thrombocytopenic purpura

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 310-315
Author(s):  
NS Szatkowski ◽  
TJ Kunicki ◽  
RH Aster
Keyword(s):  
Direct Evidence ◽  
Protein A ◽  
Normal Subjects ◽  
Platelet Membrane ◽  
Staphylococcal Protein A ◽  
Glycoprotein Ib ◽  
Thrombocytopenic Purpura ◽  
One Dimensional ◽  
Rocket Electrophoresis ◽  
And Control

An antibody (DIL) from a patient with idiopathic thrombocytopenic purpura (ITP) was shown to have autospecificity on the basis of reactions with autologous platelets that were identical to those obtained with platelets from normal subjects. DIL antibody also reacted strongly in an immunofluorescence test with platelets from a patient with Glanzmann's thrombasthenia, but failed to react with platelets from a patient with the Bernard-Soulier syndrome who was known to be deficient in glycoprotein Ib (GPIb). Purified GPIb and control platelets, but not Bernard-Soulier platelets, inhibited the lytic activity of DIL. Using the GPIb-specific monoclonal antibody AP1 and one-dimensional rocket electrophoresis into gels containing rabbit antihuman platelet membrane antibody, it was shown that staphylococcal protein A-Sepharose beads coated with DIL antibody selectively remove GPIb from solubilized platelet preparations. By crossed immunoelectrophoresis it was found that DIL recognizes a determinant on GPIb on the membrane side of the cleavage site of the platelet calcium- activated protease (calpain). These studies provide direct evidence for binding of a platelet autoantibody to a determinant on GPIb relatively close to the site of insertion of this protein into the platelet membrane.

scholarly journals Quantification of platelet-bound IgG by 125I-Staphylococcal protein A in immune thrombocytopenic purpura and other thrombocytopenic disorders

Blood ◽  
1984 ◽  
Vol 63 (1) ◽  
pp. 154-161 ◽  
Author(s):  
GM Shaw ◽  
J Axelson ◽  
JG Maglott ◽  
AF LoBuglio
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Protein A ◽  
Normal Subjects ◽  
Unknown Etiology ◽  
Staphylococcal Protein A ◽  
Thrombocytopenic Purpura ◽  
Clinical Criteria ◽  
Staphylococcal Protein ◽  
Wide Range ◽  
Immune Hemolytic Anemia

Abstract In this report we describe the use of an 125I-Staphylococcal protein A (SPA) assay to measure platelet-bound IgG in the evaluation of 62 thrombocytopenic patients. Platelets from 150 normal subjects were found to bind 146 +/- 112 molecules of SPA per platelet (mean +/- 2 SD). Nineteen of 20 patients with untreated immune thrombocytopenia had platelet IgG values above this range, with 15 of 20 having values above 1,000 molecules of SPA per platelet. Patients with immune thrombocytopenic purpura by clinical criteria, but who had failed conventional therapy (corticosteroids or splenectomy), had a wide range of platelet IgG levels: 4 of 20 had normal values, 6 of 20 had minimally elevated levels in the range seen with nonimmune thrombocytopenia, and 10 of 20 had much higher values. Fifteen patients with thrombocytopenia of apparent nonimmune origin and 7 others with chronic stable thrombocytopenia of unknown etiology were found to have platelet IgG levels within or only slightly above the normal range. Because of its simplicity, accuracy, and clinical correlation, the 125I- SPA assay provides an important new approach for studying platelet IgG in thrombocytopenic states. The data obtained with this technique are similar to those found in immune hemolytic anemia and suggest that the platelet-bound IgG so measured has pathophysiologic relevance in immune thrombocytopenic purpura.

scholarly journals Quantification of platelet-bound IgG by 125I-Staphylococcal protein A in immune thrombocytopenic purpura and other thrombocytopenic disorders

Blood ◽  
1984 ◽  
Vol 63 (1) ◽  
pp. 154-161
Author(s):  
GM Shaw ◽  
J Axelson ◽  
JG Maglott ◽  
AF LoBuglio
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Protein A ◽  
Normal Subjects ◽  
Unknown Etiology ◽  
Staphylococcal Protein A ◽  
Thrombocytopenic Purpura ◽  
Clinical Criteria ◽  
Staphylococcal Protein ◽  
Wide Range ◽  
Immune Hemolytic Anemia

In this report we describe the use of an 125I-Staphylococcal protein A (SPA) assay to measure platelet-bound IgG in the evaluation of 62 thrombocytopenic patients. Platelets from 150 normal subjects were found to bind 146 +/- 112 molecules of SPA per platelet (mean +/- 2 SD). Nineteen of 20 patients with untreated immune thrombocytopenia had platelet IgG values above this range, with 15 of 20 having values above 1,000 molecules of SPA per platelet. Patients with immune thrombocytopenic purpura by clinical criteria, but who had failed conventional therapy (corticosteroids or splenectomy), had a wide range of platelet IgG levels: 4 of 20 had normal values, 6 of 20 had minimally elevated levels in the range seen with nonimmune thrombocytopenia, and 10 of 20 had much higher values. Fifteen patients with thrombocytopenia of apparent nonimmune origin and 7 others with chronic stable thrombocytopenia of unknown etiology were found to have platelet IgG levels within or only slightly above the normal range. Because of its simplicity, accuracy, and clinical correlation, the 125I- SPA assay provides an important new approach for studying platelet IgG in thrombocytopenic states. The data obtained with this technique are similar to those found in immune hemolytic anemia and suggest that the platelet-bound IgG so measured has pathophysiologic relevance in immune thrombocytopenic purpura.

scholarly journals Experience with protein A-immunoadsorption in treatment-resistant adult immune thrombocytopenic purpura

Blood ◽  
1992 ◽  
Vol 79 (9) ◽  
pp. 2237-2245 ◽  
Author(s):  
HW Snyder ◽  
SK Cochran ◽  
JP Balint ◽  
JH Bertram ◽  
A Mittelman ◽  
...  
Keyword(s):  
Side Effects ◽  
Immune Thrombocytopenic Purpura ◽  
Protein A ◽  
Staphylococcal Protein A ◽  
Treatment Resistant ◽  
Thrombocytopenic Purpura ◽  
Specific Serum ◽  
Clinical Responses ◽  
Acute Increase

Abstract Extracorporeal immunoadsorption of plasma to remove IgG and circulating immune complexes (CIC) was evaluated as a therapy for adults with treatment-resistant immune thrombocytopenic purpura (ITP). Seventy-two patients with initial platelet counts less than 50,000/microL who had failed at least two other therapies were studied. They received an average of six treatments of 0.25 to 2.0 L plasma per procedure over a 2- to 3-week period using columns of staphylococcal protein A-silica (PROSORBA immunoadsorption treatment columns; IMRE Corp, Seattle, WA). The treatments caused an acute increase in the platelet count to greater than 100,000/microL in 18 patients and to 50,000 to 100,000/microL in 15 patients. The median time to response was 2 weeks. Responses were transient (less than 1 month duration) in seven of those patients (10%), but no additional relapses were reported over a follow- up period of up to 26 months (mean of 8 months). Clinical responses were associated with significant decreases in specific serum platelet autoantibodies (including anti-glycoprotein IIb/IIIa), platelet- associated Ig, and CIC. Thirty percent of treatments were associated with transient mild to moderate side effects usually presenting as a hypersensitivity-type reaction. Continued administration of failed therapies for ITP, which always included low-dose corticosteroids (less than or equal to 30 mg/d), had no demonstrable influence on the effectiveness of immunoadsorption treatment but did depress the incidence and severity of side effects. The degree of effectiveness of protein A immunoadsorption therapy in patients with treatment-resistant ITP is promising and further controlled studies in this patient population are warranted.

scholarly journals Heavy-chain subclass of round antiplatelet IgG in autoimmune thrombocytopenic purpura

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 84-87 ◽  
Author(s):  
K Hymes ◽  
PH Schur ◽  
S Karpatkin
Keyword(s):  
Heavy Chain ◽  
Solid Phase ◽  
Protein A ◽  
Normal Serum ◽  
Staphylococcal Protein A ◽  
Antiplatelet Antibody ◽  
Thrombocytopenic Purpura ◽  
Autoimmune Thrombocytopenic Purpura ◽  
Solid Phase Radioimmunoassay ◽  
Monospecific Antisera

Abstract The gamma heavy-chain subclass of bound antiplatelet antibody was examined in six patients with autoimmune thrombocytopenic purpura (ATP) by a solid-phase radioimmunoassay. Monospecific antisera for gamma G1, gamma G2, gamma G3, and gamma G4 subclasses were employed in a “sandwich” technique, utilizing the binding of 126I-staphylococcal protein A. We have previously reported that serum antiplatelet antibody was restricted to be gamma G3 subclass in ATP. In contrast, all 4 IgG subclasses were found bound to platelets of ATP patients in the same distribution as that present in normal serum. It is suggested that the differences noted between serum antiplatelet IgG and platelet-bound IgG may represent different mechanisms of platelet injury.

scholarly journals Heavy-chain subclass of round antiplatelet IgG in autoimmune thrombocytopenic purpura

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 84-87
Author(s):  
K Hymes ◽  
PH Schur ◽  
S Karpatkin
Keyword(s):  
Heavy Chain ◽  
Solid Phase ◽  
Protein A ◽  
Normal Serum ◽  
Staphylococcal Protein A ◽  
Antiplatelet Antibody ◽  
Thrombocytopenic Purpura ◽  
Autoimmune Thrombocytopenic Purpura ◽  
Solid Phase Radioimmunoassay ◽  
Monospecific Antisera

The gamma heavy-chain subclass of bound antiplatelet antibody was examined in six patients with autoimmune thrombocytopenic purpura (ATP) by a solid-phase radioimmunoassay. Monospecific antisera for gamma G1, gamma G2, gamma G3, and gamma G4 subclasses were employed in a “sandwich” technique, utilizing the binding of 126I-staphylococcal protein A. We have previously reported that serum antiplatelet antibody was restricted to be gamma G3 subclass in ATP. In contrast, all 4 IgG subclasses were found bound to platelets of ATP patients in the same distribution as that present in normal serum. It is suggested that the differences noted between serum antiplatelet IgG and platelet-bound IgG may represent different mechanisms of platelet injury.

scholarly journals Autoantibodies against platelet glycoprotein Ib in patients with chronic immune thrombocytopenic purpura

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 156-160 ◽  
Author(s):  
VL Jr Woods ◽  
Y Kurata ◽  
RR Montgomery ◽  
P Tani ◽  
D Mason ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Control Cell ◽  
Normal Subjects ◽  
Cell Extract ◽  
Platelet Glycoprotein ◽  
Glycoprotein Ib ◽  
Thrombocytopenic Purpura ◽  
Chronic Immune Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Negative Results

The present studies provide direct evidence that some patients with chronic immune thrombocytopenic purpura (ITP) have autoantibodies reactive with platelet glycoprotein Ib ( GPIb ). Microtiter wells coated with a monoclonal antibody that recognized GPIb were reacted with either platelet extract or a control cell extract. After washing and incubating with test plasma, well-bound IgG was quantitated using radioactive anti-IgG. When compared to plasma from normal subjects, plasma from 3 of 106 patients with chronic ITP had significantly increased quantities of IgG bound to microtiter wells reacted with platelet extracts. Negative results were obtained with the remaining 103 patients with chronic ITP and 59 patients with a variety of other platelet disorders. Plasma from two of the three positive patients precipitated a protein from 125I-surface-labeled platelet extract with a molecular weight similar to GPlb . One of the three patients with anti- GPlb antibody also had demonstrable autoantibodies to the platelet glycoprotein llb / llla complex.

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